2. Academic Validation
  3. Neuroprotective effects of GPR68 against cerebral ischemia-reperfusion injury via the NF-κB/Hif-1α pathway

Neuroprotective effects of GPR68 against cerebral ischemia-reperfusion injury via the NF-κB/Hif-1α pathway

  • Brain Res Bull. 2024 Aug 13:216:111050. doi: 10.1016/j.brainresbull.2024.111050.
Xianglong Li 1,  Kaiguo Xia 2,  Chuanhong Zhong 2,  Xiangzhou Chen 2,  Fubing Yang 2,  Ligang Chen 3,  Jian You 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China; Neurosurgical Clinical Research Center and Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, PR China; Laboratory of Neurological Diseases and Brain Functions, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China.
  • 2 Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China.
  • 3 Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China; Neurosurgical Clinical Research Center and Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, PR China; Laboratory of Neurological Diseases and Brain Functions, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China. Electronic address: ligangchen86@126.com.
  • 4 Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China; Neurosurgical Clinical Research Center and Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, PR China; Laboratory of Neurological Diseases and Brain Functions, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China. Electronic address: youjian99@swmu.edu.cn.
PMID: 39147243 DOI: 10.1016/j.brainresbull.2024.111050
Abstract

Background: G protein-coupled receptor 68 (GPR68), an Orphan Receptor, has emerged as a promising therapeutic target for mitigating neuronal inflammation and oxidative damage. This study explores the protective mechanisms of GPR68 in cerebral ischemia-reperfusion injury (CIRI).

Methods: An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. Mice received intraperitoneal injections of Ogerin, a selective GPR68 agonist. In vitro, GPR68 was overexpressed in SH-SY5Y and HMC3 cells, and the effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cell viability were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry.

Results: The expression of GPR68 was suppressed in cells subjected to OGD/R treatment, whereas its upregulation conferred protection to SH-SY5Y and HMC3 cells. In vivo, levels of GPR68 were reduced in brain tissues affected by MCAO/R, correlating with oxidative stress, inflammation, and neurological damage. Treatment with a GPR68 agonist decreased brain infarction, Apoptosis, and dysregulated gene expression induced by MCAO/R. Mechanistically, GPR68 agonist treatment may inhibit the activation of the NF-κB/HIF-1α pathway, thereby reducing oxidative and inflammatory responses and enhancing protection against CIRI.

Conclusions: This study confirms that the GPR68/NF-κB/HIF-1α axis modulates Apoptosis, inflammation, and oxidative stress in CIRI, indicating that GPR68 is a potential therapeutic target for CIRI.

Keywords

G protein-coupled receptor 68; Inflammation; Middle cerebral artery occlusion/reperfusion; Oxidation; Oxygen-glucose deprivation/reperfusion.

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